At FDA, Changes In Name Only--Agency Puts Business interests Above Safety

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[sSRI-Research] At FDA, Changes In Name Only--Agency Puts

Business interests Above Safety

 

 

 

 

 

At FDA, Change In Name Only; Legal Business; New counsel keeps

industry-friendly policies

 

ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

Promoting Openness, Full Disclosure, and Accountability

www.ahrp.org

 

FYI

 

The sudden resignation of FDA Commissioner, Lester Crawford, after

just two months in office, has prompted a bipartisan Senate

investigation and requests both by the Senate committee HELP and by

congressman Maurice Hinchey (NY) and five other members of the House

to request an investigation by the Inspector General. The New York

Times reported yesterday that Dr. Crawford may have failed to disclose

financial holdings in companies overseen by the FDA.

 

From all appearances-such as the appointment of Sheldon Bradshaw to

replace Daniel Troy as Chief Counsel, and the President's choice of a

part-time acting commissioner to replace Crawford-nothing in the

agency's culture has changed. Business interests supersede any

cosmetic gestures meant to assuage the public about increased

attention toward safety.

 

It is instructive to compare and contrast a report by Gardiner Harris

in The New York Times with one in the Legal Times assessing what

changes have actually taken place at the FDA since the spate of drug

safety scandals that revealed the agency turning a blind eye to the

mounting casualties resulting form lethal drug effects .

 

On August 6, Harris portrayed the changes-such as label

warnings-through the prism of FDA officials who consistently side with

industry, not drug safety. Dr. Scott Gottlieb, for example planted

the view that the agency's advisory committees " are vulnerable to a

growing chorus of criticism, " implying they are not persuaded by

evidence. He then planted the insidious suggestion (which Harris

dutifully reported as fact): " Now, instead of waiting for proof, the

agency has promised to issue public health alerts about drug risks

even when problems are only suspected. And over the last year, it has

demanded that pharmaceutical companies add tough warnings for drugs as

diverse as the antidepressant Zoloft, because it might lead a small

number of teenagers to become suicidal, and the popular pain pill

Advil, because it might in rare cases cause heart attacks. "

 

Gardiner Harris was badly misled by FDA officials whose concern is

clearly with business interests when he wrote that proof was needed.

In point of fact , the Food Drug and Cosmetics Act (21 CFR 201.57(e)

) REQUIRES warnings when there is reason to suspect a hazard: " the

labeling shall be revised to include a warning as soon as there is

reasonable evidence of an association of a serious hazard with a drug;

a causal relationship need not have been proved. "

 

Before the FDA came under the undue sway of industry a single

defective can of tuna fish that caused food poisoning would trigger a

recall. How then can the Times trivialize the suicide of " a small

number of teenagers " and preventable heart attacks linked to an

analgesiac?

 

Representative Maurice D. Hinchey of New York put the issue in

perspective when, referring to FDA's inaction in the face of the Vioxx

tragedy, said: " When F.D.A. goes through a 14-month-long period to get

a labeling change that both it and its panel of experts agrees is

necessary, that shows us that something is wrong. "

 

The Legal Times reports (September 19) that the legacy of Daniel Troy

who, as FDA's Chief Counsel, intervened in civil court cases on

behalf of companies such as Pfizer, continues to be followed by the

agency's new Counsel, Sheldon Bradshaw. And an analysis of the

number of compliance and warning letters shows that fewer such

letters have been issued --even as the number of corporate violations

increased. So public posturing notwithstanding, in terms of policy,

nothing has changed at the agency--business interests take priority

over safety.

 

Contact: Vera Hassner Sharav

212-595-8974

veracare

 

Senate Panel Opens Inquiry on F.D.A. Chief's Resignation

By Robert Pear: September 30, 2005

WASHINGTON, Sept. 29 - A Senate committee said Thursday that it had

opened a bipartisan investigation of the reasons for the sudden

resignation of Lester M. Crawford as commissioner of food and drugs.

The panel said it wanted to determine if Dr. Crawford had complied

with federal ethics laws and if his financial disclosure statements

had been accurate. The same Senate committee recommended confirmation

of Dr. Crawford in June.

 

The committee chairman, Senator Michael B. Enzi, Republican of

Wyoming, and the senior Democrat on the panel, Senator Edward M.

Kennedy of Massachusetts, they were examining why Dr. Crawford

resigned abruptly on Friday, with no explanation, just two months

after he was confirmed by the Senate. Mr. Enzi and Mr. Kennedy asked

for help from the new inspector general at the Department of Health

and Human Services, Daniel R. Levinson. In a letter on Thursday, the

senators said they were " examining the circumstances surrounding " Dr.

Crawford's departure, and they asked Mr. Levinson to " conduct a

thorough review of the reasons " for his resignation. " Specifically, "

they wrote, " we would appreciate if you would examine his financial

reporting in accordance with the various ethics laws to determine

whether he was in compliance and whether he was forthcoming in his

attestations to the White House counsel, the Department of Health and

Human Services, the Office of Government Ethics and the committee. "

 

 

THE NEW YORK TIMES : F.D.A. Responds to Criticism With New Caution By

GARDINER HARRIS August 6, 2005

 

Stung by a series of drug safety scandals, the Food and Drug

Administration has in recent months issued a blizzard of drug-safety

warnings and approval times for new drugs are slower. The agency is

issuing twice the number of public advisories about drug risks as it

did a year ago and adding five times as many black box warnings - its

most serious alert - to drug labels. And drugs approved in the first

half of this year took almost twice as long to get that approval as

drugs approved in the same period last year. This new conservatism, a

response to fierce recent criticism from Congress that the F.D.A. has

failed to protect the public against drug dangers, has upset some

doctors and drug makers.

 

Doctors say that the agency's vague warnings and confusing advice mean

that doctors are not getting the information they need to avoid

problems but will get blamed for them anyway. Drug makers say the

warnings are scaring patients and reducing sales. The apparent changes

have done little to mollify the F.D.A.'s many critics, who say that

the agency is either not doing enough, doing too much or failing to be

consistent. " The F.D.A. should not be slowing things down or speeding

them up depending on how the wind blows, " said Senator Charles E.

Grassley, a powerful Iowa Republican who has become one of the

agency's toughest critics. " Instead, the agency should be a rock of

stability. "

 

F.D.A. officials dismissed the notion that the agency has changed the

way it regulates drugs. " Maybe we're not being overly cautious but

instead trying to be responsive, " said Dr. Scott Gottlieb, the

agency's deputy commissioner. But Dr. Gottlieb said that the agency's

advisory committees - crucial arbiters of drug risks - are vulnerable

to a growing chorus of criticism. If the advisory committees become

more cautious, he said, the F.D.A. might follow their lead. The agency

once avoided issuing disturbing warnings about drugs unless studies

proved that a risk was certain. Agency officials had worried that

issuing warnings about suspected problems would cause undue alarm and

lead patients to stop taking needed therapies.

 

But two episodes over the last year - one involving antidepressants

and suicide risk and the other the withdrawal of the pain pill Vioxx -

have led the agency to become more cautious. Now, instead of waiting

for proof, the agency has promised to issue public health alerts about

drug risks even when problems are only suspected. And over the last

year, it has demanded that pharmaceutical companies add tough warnings

for drugs as diverse as the antidepressant Zoloft, because it might

lead a small number of teenagers to become suicidal, and the popular

pain pill Advil, because it might in rare cases cause heart attacks.

 

In each case, according to disclosures at open hearings, the agency

has acted with little or no evidence that the risks are real. But it

has demanded that warnings be placed on them anyway. In many cases,

patients have stopped taking the medicines in the wake of the

warnings. " Drug reviewers have seen that the environment has changed,

and they've become more cautious because they don't want to be the

next person hauled before Congress, " said Dr. Kenneth I. Kaitin,

director of the Tufts Center for Study of Drug Development.

 

Agency officials say that they are simply trying to do a better job of

communicating drug risks directly to doctors, pharmacists and patients

after years of letting drug makers do most of the talking. The agency

will soon issue instructions to drug companies about how to send

information by e-mail directly to physicians about drug risks, Dr.

Gottlieb said.Dr. Lester Crawford, who last month was confirmed by the

Senate to become the Food and Drug Administration commissioner, has

said that the agency can no longer wait until risk information is

proved but must communicate its uncertainty to the public. This has

left many physicians uneasy " They're just passing the blame onto the

physician if something goes wrong, " said Dr. Phillip Kennedy, a

family-practice physician in Augusta, Ga. " They're just trying to say

that they warned us. " Vague warnings about uncertain risks are

difficult for doctors to interpret, Dr. Kennedy said.

 

Dr. William Schreiber, an internist from Louisville, Ky., said that

the agency's murky and sometimes contradictory messages have hurt its

credibility. " Many of us depend on that agency to tell us that a drug

is O.K., " Dr. Schreiber said. " And when they miss the risks for a

whole category of significant drugs - and I'm still not sure whether

they're right - it makes you question the linchpins of the system. "

 

The problem is that the F.D.A. is often uncertain about how important

a potential problem with a drug might be, Dr. Kaiten said. " So, more

often than not, they just don't know what to tell physicians and

patients, " Dr. Kaiten said. When it is unsure, the agency often

advises patients to speak with their doctors, Dr. Kaiten said, " but

the physicians don't know what to tell patients, either. " Dr. Jeremy

A. Lazarus, vice speaker of the House of Delegates of the American

Medical Association, said that there is a solution. " We think there

have to be better studies done that are adequately designed and long

enough to answer these questions, " he said.

 

So far this year, the F.D.A. has issued 11 public health advisories

about drug risks compared with five in all of last year and two in

2003. In the first half of 2005, the agency placed black-box warnings

- its most serious alert - on the labels of 45 drugs compared to just

9 during a similar period last year. The agency is also taking more

time to review new drug applications. For drugs approved in the first

half of 2005, the average time from application to approval was 29

months, compared with an average of 16 months for drugs approved in

the first half of 2004. And the F.D.A. is more often asking that drug

makers study the safety of their medicines after they are approved.

 

Dr. Gottlieb explained that much of the recent increase in the number

of black-box warnings is due to the agency's decisions to place the

warnings on 33 antidepressants. He said that because the agency

processes so few new drug applications, average approval times can

change substantially from year to year because of a single difficult

application.

 

The agency's growing caution has drawn muted praise and scorn from

critics. Dr. Sidney Wolfe of Public Citizen said that the agency still

is not cautious enough. Dr. Jerry Avorn, a professor of medicine at

Harvard Medical School who for years criticized what he saw as a lack

of caution at the F.D.A., said that the agency has overreacted. " They

went from comatose to spastic without any rational period in the

middle, " Dr. Avorn said. Jack Calfee, a resident scholar at the

American Enterprise Institute who has long criticized the agency for

being overly cautious, said that its latest actions are an unfortunate

but understandable reaction to fierce public criticism. " It would be

amazing if they did not become more cautious in the wake of the Vioxx

episode, " Mr. Calfee said. Merck, the maker of the painkiller Vioxx,

withdrew the drug from the market in September after a study found

that it doubled the risks of heart attack and stroke. The Vioxx

withdrawal has been a driving force for some of the changes at the

agency. Critics in Congress pointed out in hearings that the F.D.A.

negotiated with Merck for 14 months in 2001 and 2002 before any

substantial mention of Vioxx's heart risks appeared on the drug's label.

 

" When F.D.A. goes through a 14-month-long period to get a labeling

change that both it and its panel of experts agrees is necessary, that

shows us that something is wrong, " Representative Maurice D. Hinchey,

Democrat of New York, said in a hearing last week. Dr. Steven Galson,

director of the agency's center for drugs, answered Mr. Hinchey,

" We're not proud of how long that took, let me just be clear about that. "

 

The F.D.A. does not own a drug's label, drug makers do. Short of

threatening to seize a drug if a label is not changed, the agency must

negotiate with drug makers over any changes. This can lead to delays.

Some in Congress have proposed giving the agency the power to mandate

label changes, but Dr. Crawford said that the Bush administration has

no position on these proposals.. Xxx cut..xxxx Copyright 2005 The New

York Times Company

 

Legal Times: At FDA, Change In Name Only; Legal Business; New counsel

keeps industry-friendly policies put in place by his predecessor By

Lily Henning 19 September 2005-- p. 1

Sheldon Bradshaw arrived at the Food and Drug Administration without

the baggage lugged around by his predecessor. The previous chief

counsel at the FDA, Daniel Troy, was pilloried by critics who slammed

his close ties to the drug industry. Troy made a name for himself

suing the agency on behalf of drug and tobacco companies before moving

to the government agency early in the Bush administration. Bradshaw,

who came to the FDA as chief counsel from the Justice Department in

April, has escaped that kind of scrutiny, largely because he hasn't

had those corporate relationships. But that doesn't necessarily mean a

new day has dawned.

 

In fact, despite Troy's return to the private sector, his

controversial legal policies remain in force at the agency. Like Troy,

Bradshaw offers one-on-one meetings with the companies regulated by

the agency, has kept low the number of warnings issued to companies

violating regulations, and, perhaps most notably, has continued to

intervene on behalf of drug companies in private civil lawsuits.

 

Last week, Bradshaw signed off on a brief agreeing with Pfizer Inc.'s

claim that three years ago the FDA would not have allowed the drug

company to warn consumers about a link between suicidal behavior and

the use of its best-selling antidepressant, Zoloft, by adolescents, an

argument Pfizer is using to ward off liability.

 

That approach and a lighter regulatory hand put the public at risk,

consumer and public health advocates complain. And even some in the

drug and medical-device industries find the regulatory regime under

Troy, and now Bradshaw, discomforting, claiming that without strong

FDA oversight, companies are being hauled into court more frequently

by state attorneys general and private plaintiffs.

 

" One of our clients said to me a few months ago, 'I miss the FDA,' "

says Arnold & Porter's Donald Beers, a food and drug attorney who

served as associate chief counsel for drugs and for enforcement in the

FDA's Office of Chief Counsel between 1975 and 1985. " An aggressive

FDA that occupies the stage is sometimes better than having lots of

different people sniping at you. "

 

STAYING THE COURSE

 

Before joining the FDA in April, Bradshaw was principal deputy

assistant attorney general in the Department of Justice's Civil Rights

Division. Bradshaw's move to the FDA -- generally considered a less

prestigious agency for government lawyers than the Justice Department

-- surprised some of his former colleagues, who describe him as being

part of an ideologically conservative group of young leaders in deputy

positions at the DOJ. He also worked in the Office of Legal Counsel,

made up of an elite group of lawyers at Justice who advise the

executive branch. Among the office's alumni is Troy. Both he and

Bradshaw were part of the Bush administration's advance legal teams in

2001. Bradshaw says that his lack of experience in the food and drug

regulatory arena could be, in the wake of what he says was unfair

criticism of Troy, a good thing. " I think it's helped me in my

transition that I wasn't seen as already having made up my mind on

certain issues, " Bradshaw says. " There isn't a perception that I would

have a preference in any given case. "

 

But those looking for changes to policies initiated under Troy will be

disappointed. Bradshaw says he has no intention of changing the way

the FDA's legal department does business. That continuity was evident

last Thursday, when the government filed an amicus brief in Utah

reiterating the argument championed by Troy that the FDA's

jurisdiction over prescription-drug labeling prevents plaintiffs from

suing Pfizer over Zoloft's lack of a warning label. " Wherever I go,

people ask me if I am going to continue Troy's policy in pre-emption

cases, " Bradshaw says, adding that the FDA does not take such action

by itself and must have consent from the Department of Justice and the

political leadership at the Department of Health and Human Services.

 

Troy was a pioneer of the government's intervention on behalf of

Pfizer in cases related to Zoloft and suicide, contending the FDA

would not have permitted Pfizer to warn about the suicide risk because

there was not enough scientific support for the warning. The

government's involvement began in September 2002, when Justice, joined

by the FDA, filed a friend of the court brief in the U.S. Court of

Appeals for the 9th Circuit case Motus v. Pfizer. (The 9th Circuit,

however, ultimately decided the case on different grounds, never

reaching the pre-emption issue.)

 

The argument was based on the premise that since the FDA has sole

jurisdiction over the labeling process of prescription drugs, drug

companies like Pfizer should not be held liable for warnings on

products if they follow FDA requirements.

 

The FDA's involvement in the Pfizer case sparked indignation among

interest groups, which complained that Troy, who had represented

Pfizer in private practice, was leaping to the defense of industry.

Plaintiffs advocates complain that if the FDA's legal argument in the

Zoloft case is applied broadly, then victims won't be able to sue if

they are injured by any FDA-regulated product. Pfizer has used the

2002 brief for the past three years to fend off lawsuits involving

Zoloft-related suicides.

 

In June, Judge Paul Cassell of the U.S. District Court for the

District of Utah asked the government to weigh in again, noting that

the FDA's opinion was important because the agency had injected itself

into the debate with the 2002 brief.

 

In that case -- the first in which the government has intervened since

Bradshaw took over -- the family of 15-year-old Shyra Kallas sued

Pfizer, claiming that Zoloft's label at the time their daughter

committed suicide in 2002 did not disclose the risks of suicide and

suicide-related side effects associated with the use of Zoloft in

adolescents. They also claim Pfizer failed to warn Kallas' doctor of

that possibility. Kallas, who was prescribed Zoloft by her

primary-care doctor, shot and killed herself a month after starting on

the drug. Cassell asked the FDA to explain whether the 2002 brief

would apply to the Kallas case, noting that the case involves a minor.

The drug is not approved for treatment of depression in adolescents.

And while Bradshaw calls the circumstances of the Kallas case

" tragic, " last week's filing didn't alter the position the government

held under Troy.

 

Judges have had mixed responses to the FDA's position on the Zoloft

cases, of which there are now more than a dozen nationwide. In a March

2005 decision in a federal court in Texas, in which Pfizer had filed

the 2002 amicus brief, Judge William Steger wrote that Pfizer had

relied heavily on the FDA to support its arguments. But the judge

ruled that evidence before the agency did suggest that a warning about

suicide risks was appropriate and that the FDA's regulations do indeed

allow a manufacturer to add to or strengthen a warning without prior

agency approval.

 

Karen Menzies, who represents plaintiffs in cases related to Zoloft,

notes that Pfizer never asked the FDA if it could warn consumers about

the suicide risk, adding that the FDA had information about the

suicide risk associated with antidepressants like Zoloft since the

early 1990s but did not analyze it.

 

The contention that the agency would have prevented Pfizer from

issuing the warning is " pure speculation by the FDA's attorneys, " says

Menzies, a partner with Baum Hedlund in Los Angeles. " But the sheer

weight of the FDA intervening is very persuasive. " Pfizer has

consistently denied any link between suicidal behavior and the use of

Zoloft by adolescents. Last fall, after a review of studies on risks

of suicidal thoughts and behaviors in children taking antidepressants,

the FDA directed manufacturers to add a " black box " warning -- the

most severe kind of advisory -- to the medications' labels to

emphasize the need for close monitoring of child patients taking those

drugs.

 

THE OLD ORDER

Troy, 45, is, for many critics of the Bush administration's FDA,

Exhibit A of the dangers of appointing a regulator who clashed with

the very agency in which he would later play a pivotal role. The first

appointment to the FDA made by President George W. Bush, Troy says his

was a necessarily high-profile role. As chief counsel, he gave nearly

80 speeches and met with dozens of industry groups.

 

Troy says the meetings sometimes helped to narrow the scope of

litigation against the agency and, in some situations, to avoid it.

" Sometimes when they heard our side, they said that's a good point --

or we're not going to beat you in court, " Troy says. " Sometimes I

ended up hearing their tale and decided that we were wrong. "

 

Troy was slammed by a wide range of detractors, from newspaper

editorial writers to Capitol Hill legislators, for what they said were

brazen actions benefiting the industries he represented in private

practice.

 

 

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